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IDO1 Expression Is Associated With Immune Tolerance and Poor Prognosis in Patients With Surgically Resected Esophageal Cancer

Kiyozumi, Yuki, MD*; Baba, Yoshifumi, MD, PhD, FACS*; Okadome, Kazuo, MD*; Yagi, Taisuke, MD*; Ishimoto, Takatsugu, MD, PhD, FACS*; Iwatsuki, Masaaki, MD, PhD, FACS*; Miyamoto, Yuji, MD, PhD, FACS*; Yoshida, Naoya, MD, PhD, FACS*; Watanabe, Masayuki, MD, PhD, FACS; Komohara, Yoshihiro, MD, PhD; Baba, Hideo, MD, PhD, FACS*

doi: 10.1097/SLA.0000000000002754
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Objectives: To evaluate the relationship between indoleamine 2, 3-dioxygenase (IDO1) expression and tumoral immune status and clinical outcome in esophageal cancer.

Summary Background Data: IDO1 is a primary enzyme that generates immunosuppressive metabolites such as tryptophan and kynurenine. Like the PD-1/PD-L1 pathway, IDO1 plays a major role in tumor immunology and is a potential immune-based therapeutic target.

Methods: The expressions of IDO1, CD8 (a marker of cytotoxic T cells), FOXP3 [a marker of regulatory T cells (Treg)], and PD-L1 in 305 curatively resected esophageal cancers were evaluated by immunostaining.

Results: Overall survival was significantly better in the IDO1 negative cases (n = 234) than in the IDO1 positive cases (n = 71) [log-rank P = 0.0041; hazard ratio (HR): 1.75; 95% confidence interval (CI): 1.12–2.67; P = 0.015]. CD8 high expression was significantly positively correlated with overall survival (log-rank P = 0.025) and low IDO1 expression (P = 0.044). The inverse correlation between CD8 and IDO1 expressions was confirmed by double immunostaining for IDO1 and CD8. Stratification based on IDO1 and CD8 expressions was also significantly associated with overall survival (log-rank P = 0.0024). In addition, the IDO1-positive group was correlated with high counts of FOXP3-positive cells (P = 0.020), but not with PD-L1 expression status (P = 0.19).

Conclusions: IDO1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. Combining the IDO1 and CD8 statuses enabled further classification of the clinical outcomes of patients.

*Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan

Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan

Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.

Reprints: Hideo Baba, MD, PhD, FACS, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan; E-mail: hdobaba@kumamoto-u.ac.jp.

This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, grant number 17H04273, 17K19702 and 17KK0195 (for Y.B.).

The authors report no conflicts of interest.

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